Biomarker Trio Detects Alzheimer's

Action Points

Explain to interested patients that researchers have found that a signature of three biomarkers present in cerebrospinal fluid can identify patients with Alzheimer's Disease and may be able to help predict which patients may be at risk of developing the disease.

Explain to interested patients that cerebrospinal fluid analysis to assess for these biomarkers can be useful to confirm the diagnosis of Alzheimer's Disease and decrease the likelihood of other diagnoses that might be considered, including normal pressure hydrocephalus, depression, or multi-infarct dementia.

A signature of three biomarkers can identify patients with Alzheimer's and may be able to help predict which patients may be at risk of developing the disease, researchers say.

When applying these markers -- beta-amyloid protein 1-42, total tau protein, and phosphorylated tau -- to an established data set, it accurately identified 90% of the group that had Alzheimer's disease, according to Hugo Vanderstichele, PhD, of Innogenetics in Gent, Belgium, and colleagues.

Only 39% of a control group had the signature, they reported in the August issue of Archives of Neurology.

"We have shown in this paper that there's now general acceptance that these biomarkers need to be included in official criteria to diagnose a person with dementia," Vanderstichele told MedPage Today.

Research has shown that low levels of amyloid beta and high levels of tau protein in cerebrospinal fluid are a hallmark of dementia and Alzheimer's disease.

However, the pathogenic process can precede the first symptoms of disease by 10 years or more.

So the researchers assessed the three biomarkers among 416 patients in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to determine when they could be clinically useful.

They found that this signature was present in 90% of those who had been diagnosed with Alzheimer's disease, 72% of those with cognitive impairment, and 36% of healthy controls.

"The unexpected presence of the Alzheimer's signature in more than a third of cognitively normal subjects suggests that Alzheimer's disease pathology is active and detectable earlier than has heretofore been envisioned," the researchers wrote.

They saw many of the healthy controls with the Alzheimer's signature were ApoE4 carriers.

Vanderstichele said this test could be applied when patients are first presenting with memory problems.

"You can make a distinction -- is this related to [another factor] or is this a real, ongoing brain disease like Alzheimer's," he said. "You can also exclude normal Alzheimer pathology and can identify whether or not a person is really progressing to Alzheimer's."

The researchers verified their results in two other data sets. In one analysis among 68 autopsy-confirmed cases of Alzheimer's disease, 94% of patients were correctly classified with the Alzheimer's signature.

Another data set with 57 patients who had mild cognitive impairment and were followed for five years showed a sensitivity of 100% in patients progressing to Alzheimer's.

"They can use the cerebrospinal fluid biomarker profile together with a clinical battery to have proof-of-concept that they really have an Alzheimer's patient or a patient who will progress to Alzheimer's disease in the near future, within five or 10 years," Vanderstichele said. "You have a much better objective indication of what is happening in the brain."

In an accompanying editorial, A. Zara Herskovits, MD, PhD, of Brigham and Women's Hospital, and John H. Growdon, MD, of Massachusetts General Hospital, said the report "solidifies the diagnostic importance of measuring amyloid beta, total tau, and phosphorylated tau in cerebrospinal fluid, and confirms the value of cerebrospinal fluid measurements in predicting the conversion of mild cognitive impairment to Alzheimer's disease."

Herskovits and Growdon added that cerebrospinal fluid analyses haven't been a routine part of assessment and care for patients with cognitive impairments and suspected Alzheimer's, but "there is now ample evidence that these measurements have value."

"Physicians need to formulate when and how to incorporate cerebrospinal measurements into their practice," they wrote.

The study was supported by an Alzheimer's Disease Neuroimaging Initiative grant.

Vanderstichele and two co-authors are employees of Innogenetics, maker of the cerebrospinal fluid assays used in the study.

Geert De Meyer, PhD, was a former employee of Innogenetics, which is now part of Solvay-Pharma.

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